New effective therapies are greatly needed for ocular and advanced cutaneous melanomas which currently have high mortality rates. The melanocortin 1 receptor (MC1R) is expressed in ocular and metastatic melanomas and we have developed a novel-targeting molecule called melanocortin 1 receptor ligand (MC1RL) that binds with very high affinity to MC1R. We have already shown that imaging contrast agents can be attached to MC1RL and specifically delivered to melanoma tumors in mice. These tumors retain the targeted payload at high levels, but the agents are otherwise rapidly cleared from the animals. This is important because it suggests that the radiotherapeutic analog will be selectively retained in melanoma tumors and metastases, but not be retained in tissues of concern for toxicity. Encouraged by these results, we attached 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA) to the MC1RL to make (DOTA-MC1RL), chelated the therapeutic radionuclide Ac-225, demonstrated high binding affinity to MC1R-expressing cells, ?97% radiosynthesis yield, ?99.8% radiochemical purity and 90% biostability after 10 days in plasma at 37C. These results are exceptional. The goal of this application is to generate preliminary data needed to launch the commercial development of this MC1RL targeted radiotherapeutic agent as a much needed treatment for ocular and metastatic melanoma.